EINet Alert ~ Sep 25, 2009

*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and
notifications for emerging infections affecting the APEC member economies. It
was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:

China
The Chinese Ministry of Health said on its website that 1,319 more patients were confirmed to have H1N1 influenza. Of those cases, 1,312 occurred in the Chinese mainland, while 7 others were infected overseas. The announcement brings the number of confirmed cases on the Chinese mainland to 14,581.

Hong Kong
Yesterday [23 Sep 2009], 677 more patients in Hong Kong were confirmed to have H1N1 influenza, raising the total number of confirmed cases there to 23,898. With 18 of the cases occurring among students, the Hong Kong health bureau suggested classes be suspended for the time being.

Thailand
The Thai Ministry of Public Health confirmed 23 Sep 2009 that 7 more patients died of H1N1 influenza last week, bringing the country's death toll from the virus to 160 since the outbreak began 28 Apr 2009.

Viet Nam
Vietnamese officials confirmed Viet Nam's 10th death from H1N1 influenza. 194 new H1N1 influenza cases were reported, 120 in the south, 46 in the north, 6 in the central region, and 22 in the Central Highlands. There have now been 7,636 confirmed cases of H1N1 infection, with 56 of the 63 provinces and cities reporting cases.

In the temperate regions of the northern hemisphere, influenza activity remains widely variable. In North America, the United States is reporting increases in influenza-like-illness activity above the seasonal baseline, most notably in the southern, southeastern, and parts of the northeastern United States.

In the tropical regions of the Americas and Asia, influenza transmission remains active. Geographically regional to widespread influenza activity continues to be reported throughout much of South and Southeast Asia, with increasing trends in respiratory diseases being reported in India and Bangladesh. Geographically regional to widespread influenza activity continues to be reported for the tropical regions of Central and South America without a consistent pattern in the trend of respiratory diseases (continued increases are being reported in Bolivia and Venezuela).

In the temperate regions of the southern hemisphere, influenza activity continues to decrease or has returned to the seasonal baseline in most countries. In Australia, later affected areas are also now reporting declining levels of influenza-like-illness. In South Africa, influenza activity appears to have recently passed over the second peak (the first peak was due to seasonal influenza A (H3N2) and second peak was due to pandemic (H1N1) 2009).

WHO Collaborating Centers and other laboratories continue to report sporadic isolates of oseltamivir resistant influenza virus. Twenty six such virus isolates have now been described from around the world, all of which carry the same H275Y mutation that confers resistance to the antiviral oseltamivir but not to the antiviral zanamivir. Of these, 12 have been associated with post-exposure prophylaxis, five with long term oseltamivir treatment in patients with immunosuppression. Worldwide, over 10,000 clinical samples and isolates of the pandemic (H1N1) 2009 virus have been tested and found to be sensitive to oseltamivir. WHO will continue to monitor the situation closely in collaboration with its partners.

Pandemic (H1N1) influenza virus continues to be the predominant circulating influenza virus, both in the northern and southern hemisphere.

WHO applauds and welcomes the announcement of donations of pandemic vaccine made today by the United States of America, in concert with Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, and the United Kingdom. Given that current demand outstrips supply, these donations, together with the doses pledged by manufacturers, will help increase supplies of pandemic vaccines to populations that would otherwise not have access.

The World Health Organization scaled back its estimate of how many doses of pandemic vaccine that producers will likely make over the next year and said it hopes to gather enough vaccine donations to cover about 10% of developing countries' populations. These details about the WHO's efforts to collect vaccine donations for developing countries came the same day that the United Nations (UN) released a report detailing the urgent support needed to help developing countries respond to the pandemic.

Today [24 Sep 2009] at a press conference, Dr Marie-Paule Kieny, the WHO's director of vaccine research, said the latest assessments indicate vaccine makers will make 3 billion doses over the next year, which would cover less than half of the world's population of 6.8 billion people. Kieny said the WHO based its original estimate of global pandemic vaccine production on a survey it conducted in May of 26 manufacturers that indicated a willingness to make pandemic H1N1 vaccine. Some of the original assumptions weren't realistic, she said.

Despite decreased projections, there are several promising vaccine developments, Kieny said. For example, a handful of countries, including China and the United States, have already approved pandemic H1N1 vaccines, and China is already administering the vaccine, with other countries, such as Hungary, soon to follow. She also added that clinical trial findings showing that most people will need only one dose of the vaccine will help stretch the world's supply.

Developing countries will likely start receiving their first doses at the end of October or in November, Kieny told the media. The WHO said it will distribute about 300 million doses of vaccine to more than 90 countries. Two vaccine makers have already donated 150 million doses to developing countries, and on Sep 17 the United States and eight other nations announced they would share some of their vaccine supply as doses come available. Kieny projected that the donations from the countries would total 50 million doses, though she said she anticipates that more countries will sign on to the donation push. She added that the WHO could round out the supply by purchasing vaccine from manufacturers that have offered a discount for developing countries.

The earliest results from testing of a pandemic H1N1 vaccine in children suggest that older children will get a good immune response with a single dose, but children younger than 10 are likely to need two doses a few weeks apart, US health officials said 21 Sep 200. The early findings, based on blood samples taken 8 to 10 days after vaccination, demonstrate a response "strikingly similar" to children's responses to seasonal flu shots, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), which sponsored the trial.

Seventy-six percent of children between 10 and 17 years old had a strong immune response to a single injection of vaccine made by Sanofi Pasteur. But, according to Fauci, among 3- to 9-year olds, the proportion with a good immune response (hemagglutination inhibition titer of 1:40) dropped to 36%, and in children between 6 and 35 months old it was 25%. Fauci said the data suggest that one dose would be enough to generate a protective immune response in 10- to 17-year-olds but that younger children may need two doses, depending on their health history.

Although trial results for the nasal-spray (live attenuated) vaccine have not yet been announced, Dr Jesse Goodman of the Food and Drug Administration (FDA) said today [21 Sep 2009], "I think it is likely that younger children may need a second dose with that vaccine as well."

Another NIAID-sponsored trial is looking at children's responses to H1N1 and seasonal flu vaccines when given at the same time or sequentially. Fauci said it will probably take until November to get "meaningful" results from that trial.

The World Health Organization (WHO) has recommended that seasonal influenza vaccines for use in the southern hemisphere next year contain the pandemic H1N1 virus instead of a current seasonal H1N1 strain, signaling that the pandemic strain is expected to push the older H1N1 strains aside. The WHO also picked a new strain of influenza A/H3N2 for the 2010 Southern Hemisphere vaccine, while keeping the influenza B strain the same. The recommendation means that manufacturers will likely be changing two of the three strains used in the vaccine.

The WHO annually recommends one H1N1, one H3N2, and one B strain for use in seasonal flu vaccines, trying to match the current circulating strains. The three recommended flu strains are normally combined in one vaccine, but the WHO said it was not ready to decide whether the three newly recommended strains should be combined or if separate seasonal and pandemic vaccines should be used next year in the southern hemisphere. "WHO will be in a position to provide guidance on this issue after the Strategic Advisory Group of Experts (SAGE) meets in late October and deliberates on this issue," the agency said.

The three strains recommended by the WHO are:

For pandemic H1N1, an A/California/7/2009-like virus (the strain used in the current pandemic vaccines)

A large outbreak of pandemic H1N1 influenza has been reported on a farm in Northern Ireland. There were 4,500 cases among 5,000 susceptible pigs with 0.1% of susceptible animals lost through death, destruction and/or slaughter. Suspected cases were confirmed by real-time PCR [16 Sep 2009], gene sequencing [17 Sep 2009] and PCR [17 Sep 2009]. No known cases of human influenza are currently associated with this outbreak.

A pandemic H1N1 influenza vaccine has been approved by the Therapeutic Goods Administration (TGA), federal Health Minister Nicola Roxon has confirmed. The vaccine, developed by pharmaceutical firm CSL, will be available later in September. Ms Roxon said there was enough vaccination available for all adults.

The vaccination program would be the largest in the nation's history with the initial rollout to focus on protecting frontline health workers and those most at risk. "The priority groups for vaccination are frontline healthcare and community care workers who have direct contact with patients, people with underlying medical conditions such as asthma, cancers, HIV, heart disease, diabetes and chronic kidney failure." Ms Roxon said people who are obese, indigenous Australians, children in special schools aged over nine, pregnant women and parents and guardians of children aged up to six would also receive priority care.

The first wave of H1N1 vaccine will probably consist of 3.4 million doses of MedImmune's nasal-spray product and is likely to reach providers the first week in October, federal health officials said. Previously the general expectation was that the first doses wouldn't be available until mid October. The vaccine will be allocated to states in proportion to their population. The CDC expects about 90,000 sites to participate in the campaign, some of which may be retail chains that further redistribute vaccine to their outlets.

According to Dr. Jay Butler, head of the CDC H1N1 Vaccine Task Force, "In any given location the availability of the vaccine may actually vary. So oftentimes that decision of who is actually administered the vaccine may ultimately be decided by the provider and the patient."

The CDC has been predicting that about 45 million to 50 million doses of vaccine will become available in mid October, followed by about 20 million a week after that, reaching a total of 195 million in December. Butler reaffirmed that forecast today.

On the final day of a business preparedness summit in Minneapolis, a panel of experts emphasized having clear, open communication with employees as well as having flexible plans—lessons they learned from being on the frontlines during the spring novel H1N1 outbreak. Other critical lessons shared by the panelists were the need to build strong relationships between corporations and national and local governments and recognizing the importance of promoting prevention measures both in and outside of the workplace.

The 2-day summit, "Keeping the World Working during the H1N1 Pandemic," was sponsored by the CIDRAP Business Source, part of the University of Minnesota Center for Infectious Disease Research and Policy.

Building strong relationships
"The single most important thing that we learned is that government trumps everything," said Fred Palensky, PhD, chief technology officer with the 3M Company in St. Paul. Despite the fact that 3M had planning policies in place for crises, such as a flu outbreak, that could disrupt their businesses, these didn't matter once the government mandated policies to shut down schools and prohibit people from going to work.

One critical lesson Palensky learned from his company's experience is the importance for businesses to develop a strong relationship with national and local governments, particularly when there is a lot of conflicting information about what is occurring. It is important, he said, to try to have access to the highest levels of government to get a consensus of what is going on.

Other critical relationships to form are with people who have expertise in pandemic preparedness. Palensky said that, along with having a corporate medical director with pandemic planning expertise, the company also works with local medical experts.

Maintaining good communication
This often-conflicting information in the spring highlighted the need for developing and maintaining good communication with employees. "Everyone had a different story, and there was no reliable data," said B. Rodrigo Cabanilla, MD, corporate medical director of occupational medicine with the Monsanto Company. As a result, his company is now trying to implement a way to obtain and disseminate information to its employees as quickly as possible.

One important aspect of developing good communication with employees is to identify high-risk patients, according to Cabanilla. Highlighting that 99.5% of employees who get sick will only be mildly affected and return to work, he stressed the importance of "attending to and identifying as soon as possible high-risk people and provide interventions."

Taking care of families
Dr. Irene Lai, MB, BS, deputy medical director of International SOS in Sydney, Australia, highlighted the importance of taking care of employees' families. She said that, particularly with the expatriate population, employees are concerned about protection of their families. Therefore, early on International SOS communication efforts and decisions included how employee behavior is modified by families.

BioCryst Pharmaceuticals said it received a request for proposal (RFP) from the U.S. Department of Health & Human Services for the supply of its experimental intravenous drug, peramivir, to treat critically ill influenza patients under emergency use authorization (EUA). The company also said it received an additional $77.2 million from the department to complete late-stage development of peramivir.

MedImmune announced that the U.S. Department of Health and Human Services (HHS) has placed an order for an additional 29 million doses of its live attenuated influenza vaccine (LAIV) against the 2009 H1N1 influenza virus. This brings HHS orders to date to more than 40 million vaccine doses. Previous HHS orders for approximately 13 million doses of LAIV for the 2009 H1N1 strain were placed in May and July.

The Ministry of Health of Egypt has reported 2 new confirmed human cases of avian influenza A(H5N1). Both cases, a 13-year old male and a 14-month old female, received oseltamivir treatment and are in stable condition. Investigations into the source of infection indicated that both cases had close contact with dead and/or sick poultry. The cases were confirmed by the Egyptian Central Public Health Laboratories. Of the 87 cases confirmed to date in Egypt, 27 have been fatal.

Data selection. Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias.

Data synthesis. 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure—that is, the higher the risk the longer the distancing period.

Conclusion. Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.

Summary. Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15–1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

Q&A: What have we found out about the influenza A (H1N1) 2009 pandemic virus?Turner SJ, Brown LE, Doherty PC, Kelso A. J Biol. 2009 Sep 18;8(8):69. [Epub ahead of print]. Available at http://jbiol.com/content/8/8/69.

Stephen Turner and colleagues follow up their earlier Q&A on influenza A (H1N1) 2009 and ask what we now know about its transmissibility, pathogenicity and variability, and the likelihood of more severe disease in the Northern hemisphere winter.

4. NotificationsAPEC EINet “Hot Topics” Video Conference: Lessons Learned from the First WaveAPEC EINet is currently actively organizing a videoconference on pandemic influenza: “Pandemic H1N1 preparedness: lessons learned & preparing for the second wave”. The videoconference is set for 4 Nov 2009 Americas time and 5 Nov 3009 Asia time. The session will feature case studies to discuss how preparedness plans affected the response to pandemic influenza, what worked, did not work, and what could be changed for a more effective response in the future. Participating economies are: Australia, Canada, Mexico, Philippines, Singapore, Chinese Taipei, and the USA.

The purpose is to create an Ad Hoc multi-sector Crisis Management Consortium during the event, to be studied as a model by communities worldwide. It is the first world event to invite leaders representing every sector of society to model a community process to help prepare, respond, and recover from a localized outbreak, as well as broader pandemic. Additional information and registration available at
>http://wrcgo.eve-ex.com/.

The 16th ISHEID Symposium on HIV & Emerging Infectious Diseases will take place in Marseille, France, from 24 to 26 March, 2010. Tackling each topic from basic science to clinical applications, this meeting will deal with issues of HIV/AIDS, Viral Hepatitis, Emerging Infectious Diseases, and welcome many Key Opinion Leaders.